Drug resistance invariably develops over the course of continuing chemotherapy. Overcoming this problem is a major challenge in the treatment of cancer. Indeed, tumor cells utilize multiple mechanisms to increase their resistance to chemotherapeutic drugs. For example, tumor cells may overexpress the multiple drug resistant transporter and oncoprotein epidermal growth factor receptor genes, as well as induce the activity of NF-E2-related factor 2, a redoxsensing transcription factor that upregulates a wide spectrum of genes involved in glutathione metabolism and drug detoxification. See (Huang et al., 2005a; Makarovskiy et al., 2002; Wang et al., 2010); (Salzberg et al., 2007; Sirotnak et al., 2000); (Singh et al., 2010; Zhang et al., 2010); and (Huang and Sadee, 2003; Seruga et al., 2010). The Hedgehog pathway is another cell signaling pathway that is involved in chemoresitance. (DomingoDomenech et al., 2012).
To date, no single agent that was designed to target a specific mechanism of resistance has been found to be effective. However, one potential source of novel therapies for addressing drug resistance are traditional Chinese herbal medicines. Indeed, such medicines have been used for thousands of years to restore imbalances of body functions that result from a multitude of diseases. Treatment with herbal medicines usually involve ingestion of a herbal “extract” that contains multiple chemical components that can potentially act at different sites and pathways in the body. Thus, these medicines have the potential to target multiple cellular and molecular mechanisms that may offer a new opportunities in overcoming drug resistance, or simply improve the efficacy of drugs. See Chow & Huang 2010, Pon et al 2010. As described herein, an ethanol extract from one particular traditional Chinese medicinal herb, Triperygium wilfordii, which is also known by its Chinese (Mandarin) name, Lei Gong Teng, sensitizes cancer cells that have become resistant to chemotherapeutic drug therapy, so that the cancer once again becomes sensitive to the chemothearpeutic drug.